The Prognostic Significance of Diabetes and Microvascular Complications in Patients With Heart Failure With Preserved Ejection Fraction

Background

Almost half of patients with heart failure with preserved ejection fraction (HFpEF) also have diabetes mellitus (DM), which is associated with nearly a twofold increase in morbidity and mortality in these patients [1-3]. Diabetes is, however, not a uniform disorder, and the risk of adverse CV outcomes may vary with disease severity (e.g., presence of microvascular complications).

In this analysis of the TOPCAT study [4], the prognostic significance of DM and its microvascular complications was evaluated in 3,385 patients with symptomatic HF and an EF ≥45%. The microvascular complications included neuropathy, nephropathy, and retinopathy, and the study outcome was the composite of CV mortality, aborted cardiac arrest, or HF hospitalization

Main results

During a median follow-up of 3.4 years, a total of 1,524 hospitalizations, 437 hospitalizations for HF, 516 deaths, and 330 CV deaths occurred. 1109 Patients (32%) of the patients included in this analysis had diabetes.

95%CI 1.22, 2.45; P-trend = 0.0017), and CV death (HR 1.70, 95% CI 1.09, 2.65, P-trend = 0.018) was observed in patients with diabetes and microvascular complications as compared with patients without diabetes. Patients with diabetes without microvascular complications also showed a higher risk of these events but to a lesser extent.

When the analysis was limited to DM participants who reported prior hospitalization for HF, a higher risk of re-hospitalization for HF was observed in patients with as compared with those without microvascular complications (HR for DM without microvascular complications: 1.40; 95% CI: 1.01 - 1.96; HR for DM plus microvascular complications: 1.78; 95% CI: 1.18 - 2.70; P-trend = 0.0036).

In a secondary analysis (model corrected for multiple CV risk factors and medications) limited to persons with DM, a higher risk of hospitalization (with no complications as references: HR: 1.29 for those with 1 complications, HR: 1.57 for those with ≥2 complications, P-trend <0.001), HF hospitalization (HR: 1.20 [non-significant) and HR: 1.63 respectively, P-trend = 0.0063), and death (HR: 1.24 [non-sign) and HR: 1.49 respectively, P-trend = 0.037) was observed with a higher number of microvascular complications.

The risk of CV death did not increase with a higher number of microvascular complications (non-significant HR: 1.31 and 1.27 for 1 and ≥2 microvascular complications, respectively, P-trend = 0.45).

Conclusion

In the TOPCAT study, diabetes and its microvascular complications carried important prognostic information regarding adverse outcomes in HFpEF patients. In addition, the microvascular disease burden predicts HF re-hospitalization in this high-risk group. These findings show that additional preventive strategies to reduce morbidity and mortality in HFpEF patients with DM are needed.